MC# 21-45 - A Phase I Study of SY-5609, an Oral, Selective CDK7 Inhibitor, in Adult Patients with Select Advanced Solid Tumors

  • Agent(s): SY-5609
  • Disease Type(s): Pancreatic
  • Phase(s): I
  • Drug Classification(s): Small Molecule, Targeted Therapy
  • Molecular Target(s): CDK7

Mechanism of Action

SY-5609 is a potential selective, oral CDK7 inhibitor.  CDK7 inhibition has been shown to target two fundamental processes in cancer: transcription and cell cycle control.

Purpose

In this study, the sponsor and investigators want to learn:

  • How much of SY-5609 can be given in combination with Gemcitabine and/or nab-Paclitaxel with an acceptable level of side effects
  • The effects of SY-5609 in combination with Gemcitabine and/or nab-Paclitaxel (good and bad)
  • How much of SY-5609 is absorbed into the blood and how fast it is removed
  • If research tests can be used in the future to predict who will benefit from SY-5609
Inclusion Criteria
  1. Age ≥ 18 years
  2. Diseases for which standard curative or palliative measures do not exist or are no longer effective, including:
    • Patients Enrolled into SY-5609 + Gemcitabine Combination (Group 3)
      • Histologically or cytologically confirmed PDAC with measurable metastatic lesion(s), as confirmed by computed tomography (CT) or magnetic resonance imaging (MRI), according to RECIST v1.1 
      • Second- or third-line patients with relapsed/refractory disease after FOLFIRINOX or modified FOLFIRINOX chemotherapy treatment for metastatic disease (prior gemcitabine-based therapy is permitted)
    • Patients Enrolled into SY-5609 + Gemcitabine + Nab-paclitaxel Combination (Group 4)
      • Histologically or cytologically confirmed PDAC with measurable metastatic lesion(s), as confirmed by CT or MRI, according to RECIST v1.1
      • Second-line patients with relapsed/refractory disease after FOLFIRINOX or modified FOLFIRINOX first-line chemotherapy treatment for metastatic disease
  3. ECOG performance status of 0 or 1 and life expectancy > 3 months (as assessed by the Investigator)
  4. Patients must have at least 1 measurable lesion by RECIST v1.1
  5. All toxicities from prior cancer treatments must have resolved to ≤ Grade 1 before enrollment except for alopecia, and for acquired endocrine disorders post immunotherapy that have resolved to ≤ Grade 2 with appropriate hormone replacement therapy
  6. Adequate organ and marrow function
  7. For women of childbearing potential (WCBP): negative serum β human chorionic gonadotropin pregnancy test within 1 week before the first dose of SY-5609 (WCBP are defined as sexually mature woman who have not undergone surgical sterilization or who have not been naturally postmenopausal for at least 12 consecutive months for women > 55 years of age)
  8. Willingness of female patients who are not surgically sterile or postmenopausal to use medically acceptable methods of birth control for the duration of the study treatment, including 30 days after the last dose of SY-5609. Willingness of male patients who are not surgically sterile to use medically acceptable methods of birth control for the duration of the study treatment, including 30 days after the last dose of SY-5609. Sexually active men, and women using oral contraceptive pills, should also be willing to use barrier contraception.
  9. Willing and able to comply with all aspects of the protocol
  10. Provide written informed consent before any study-specific screening procedures
  11. Albumin ≥ 3.0 g/dL
Exclusion Criteria
  1. Chemotherapy or limited field radiotherapy within two (2) weeks, wide field radiotherapy within four (4) weeks, or nitrosoureas or mitomycin C within six (6) weeks before entering the study
  2. Major surgery within two (2) weeks before starting the study treatment, or not recovered to baseline status from the effects of surgery received > two (2) weeks prior
  3. Received any other investigational agents within 4 weeks before enrollment, or < five (5) half-lives since completion of previous investigational therapy, whichever is shorter
  4. Received previous noncytotoxic, US Food and Drug Administration-approved anticancer agent within previous two (2) weeks, or < five (5) half-lives since completion of previous therapy, whichever is shorter
  5. Known brain metastases or carcinomatous meningitis
  6. Immunocompromised patients with increased risk of opportunistic infections
  7. Patients with known active or chronic hepatitis B or active hepatitis C infection.  Patients with a history of hepatitis C virus (HCV) infection who have completed curative therapy for HCV at least 12 weeks before Screening and have a documented undetectable viral load at Screening are eligible for enrollment.
  8. Baseline QT interval corrected (QTc) with Fridericia's method > 480 ms
    • NOTE: criterion does not apply to patients with a right or left bundle branch block (QTc interval)
  9. Female patients who are pregnant or breastfeeding
  10. History of clinically significant cardiac disease or clinically relevant uncontrolled cardiac risk factors
  11. Uncontrolled intercurrent illness
  12. Poorly controlled ascites requiring paracentesis within 1 month prior to entering the study

Location

  • Dallas, TX - Mary Crowley Cancer Research - Medical City
More Info: https://clinicaltrials.gov/ct2/show/NCT04247126

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Re: MC# 21-45